Zolpidem for persistent insomnia in SSRI-treated depressed patients

Background: Depressed individuals effectively treated with selective serotonin reuptake inhibitors (SSRIs) often report persistent insomnia and require adjunctive sleep-promoting therapy. Method: Men (N = 40) and women (N = 150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment (at least 2 weeks) with fluoxetine (less than or equal to 40 mg/day), sertraline (less than or equal to 100 mg/day), or paroxetine (less than or equal to 40 mg/day) for DSM-IV major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of less than or equal to 2 on item 3 of the Hamilton Rating Scale for Depression [HAM-D]) participated in this randomized, double-blind, parallel-group study. At study entry, patients were required to score less than or equal to 12 on the HAM-D. During a 1-week single-blind placebo period, patients had to report on at least 3 nights a latency of greater than or equal to 30 minutes or a sleep time of < 6.5 hours and clinically significant daytime impairment. Patients received either placebo (N = 96) or zolpidem, 10 mg (N = 94) nightly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep was measured with daily questionnaires and during weekly physician visits. Results: Compared with placebo, zolpidem was associated with improved sleep: longer sleep times (weeks 1 through 4, p <.05), greater sleep quality (weeks 1 through 4, p <.01), and reduced number of awakenings (weeks 1, 2, and 4; p <.05), together with feeling significantly more refreshed, less sleepy, and more able to concentrate. After placebo substitution, the zolpidem group showed significant worsening relative to pretreatment sleep on the first posttreatment night in total sleep time and sleep quality, reverted to pretreatment insomnia levels on the other hypnotic efficacy measures, or maintained improvement (fewer number of awakenings). There was no evidence of dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates of adverse events were similar in both treatment groups (74% and 83% for placebo and zolpidem, respectively), but 7 zolpidem patients discontinued compared with 2 placebo patients. Conclusion: In this defined patient population, zolpidem, 10 mg, was effectively and safely coadministered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being.